Limited tumour progression beyond Milan criteria while on the waiting list does not result in unacceptable impairment of survival.

ABSTRACT Background & Aims Defining optimum management of patients progressing beyond Milan criteria on the waiting list is a controversial topic. Our aim was to determine whether the policy of allowing a limited progression beyond enlistment criteria permits acceptable outcomes in terms of survival and recurrence. Methods Patients with hepatocellular carcinoma included on the waiting list for liver transplantation (OLT) between January 1989 and December 2016 were analyzed. Tumour features were assessed at inclusion on the waiting list, before OLT and at explant pathology. Patients were retained on the waiting list despite exceeding enlistment criteria if not presenting macrovascular invasion, extrahepatic spread or cancer-related symptoms. Results A total of 495 patients constituted the target population. Comparison between Milan-in (n=434) and Milan-out group (n=61) whilst transplanted showed statistically significant differences in: largest tumour size; BCLC stage; patients treated before OLT; α-fetoprotein, and time on waiting list. Milan-out patients showed a significantly higher number of poorly differentiated nodules, satellitosis and microscopic vascular invasion. The 1,3,5 and 10-year survival rate was 89.6%, 82.5%, 75%, and 55.5%, vs. 83.6%, 70.5%, 65.5%, and 53.9% for Milan-in/Milan-out patients, respectively. Recurrence rate at 1,3,5 and 10 years was 1.2%, 3.3%, 5.5%, and 10.8% vs. 7.1% 14.5%, 23%, and 23% for Milan-in and Milan-out patients, respectively (p Conclusion This study shows that although limited tumour progression without reaching major adverse predictors (vascular invasion, extrahepatic spread, cancer symptoms) has an expected impact on recurrence rate, overall survival remains above the minimum proposed benchmark of 65% at five years. The clinically relevant increase in tumour recurrence must be taken into account when analysing the benefit of this approach in the case of a limited organ supply. Lay Summary Optimum results are indeed obtained for hepatocellular carcinoma (HCC) patients following orthotopic liver transplantation (OLT) when the Milan criteria (MC) are used. However, the most appropriate strategy in cases of progression beyond MC while on the waiting list is still unclear. Herein, we present 27 years’ experience in OLT for HCC, using a conservative approach for those who progress beyond MC while still continuing enlistment for OLT. Although the survival in Milan-out patients is in accordance with previous published studies, the recurrence rate was notably higher. Therefore, the assessment of transplantation viability in those patients has to take into account the availability of organs and the impact on other patient categories.